Summary / Abstract This is an application for funding to replace and upgrade an IVIS 200 optical imaging system that has been in use for 12 years at Vanderbilt University for diverse fluorescent and bioluminescent studies of mice and small rats in vivo. The upgrade to an IVIS Spectrum system (a replacement which includes a sensitive optical imaging system, computer, and anesthesia modules) is required (a) because after 12 years the IVIS 200 system is no longer state-of-the-art and its performance limits ongoing research projects but also (b) the manufacturer (now owned by PerkinElmer) will no longer (since 2014) maintain crucial hardware components or support the system in a satisfactory way. The upgrade will ensure the continuing productivity of this important resource, and at the same time provide enhanced capabilities. This device has been used by over 80 established investigators over the past 5 years, and in this application we feature a selected 19 investigators all of whom are experienced users of the current IVIS 200 scanner, in a variety of research applications and training programs. These research projects fall into 4 main categories: (1) Molecular imaging probe development, the production of new and improved optical imaging probes, along with applications in small animals; (2) Cancer, and the development and applications of bioluminescence and fluorescence imaging for the study of tumor biology in small animal models, including the development of imaging biomarkers to assess novel treatments for cancer; (3) Neuroscience, and the application of optical imaging to studies of the brain, especially the effects of specific genetic modifications and of novel pharmaceuticals; (4) Metabolic Disorders, and the development and applications of optical imaging methods to studies of physiology and biochemistry in vivo. The projects of 12 Major Users would require approximately 65% use of the instrument, the listed 8 Minor Users would require about 25% of the time, and the remaining time available would be available for exploratory research and new directions. There are a much larger number of investigators who are also minor users. Each of the projects will benefit from the advantages of the IVIS Spectrum system, including the ability to acquire co-registered bioluminescence and fluorescence tomographic images on a single system; spectral unmixing algorithms to minimize autofluorescence and image multiple fluorescent probes simultaneously; and transillumination excitation geometry for detecting and quantifying deep tissue fluorescent sources. The IVIS Spectrum will be housed and managed within the Vanderbilt University Institute of Imaging Science (VUIIS), and will remain a primary research resource for a large group of imaging scientists and trainees. The instrument will be supported by an established group of optical imaging experts and support staff. A comprehensive plan has been developed for the financial and technical support of the system as well as for its management and use, and the system is assured of strong institutional support and oversight.